Lin Yang, Xiaoqian Zhou, Junfeng Hu, Ziyu Jia, Shuyun Jiang, Dan Xu, Zhijie Dan
As revealed by the results, hepatic mitochondrial impairment was induced in turbot by oxidized fish oil ingestion, as reflected by reduced cristae number, cristae disorganization, and concentric cristae formation, while a significant increase in hepatic superoxide anion abundance was also noted (P < 0.05). These mitochondrial alterations were partially alleviated by genistein supplementation, with which a marked decrease in superoxide anion levels was concurrently observed (P < 0.05). Moreover, the hepatic mRNA levels linked to inflammation, oxidative stress, and apoptosis were markedly upregulated in the OFO group (P < 0.05), yet declined in the GEN40 group (P < 0.05). Transcriptomic analysis revealed that after genistein supplementation in oxidized fish oil-based diets, the DEGs were predominantly enriched in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways such as the Peroxisome Proliferator-Activated Receptor (PPAR), calcium signaling, and adrenergic signaling pathways. It was further revealed by Gene Ontology (GO) enrichment analysis that the OFO group chiefly suppressed lipid catabolism and signal transduction, while activating the immune response. Compared with the FFO group, the genistein-treated group downregulated lipid metabolism and upregulated substance transport processes. Relative to the OFO group, it downregulated signal transduction and upregulated RNA-related catalytic activities. Moreover, methionine-S-sulfhydryl reductase B2 (msrb2) and heat shock protein 60 (hspd1) were identified as hub genes through Weighted Gene Co-expression Network Analysis (WGCNA) and were associated with the genistein-mediated alleviation of hepatic oxidative and inflammatory stress that was triggered by oxidized fish oil in turbot.
INTRODUCTION: Extensive investigations have been conducted across mammalian species to explore the redox-modulating and inflammation-resolving properties of genistein and the mechanisms involved; however, research on the functions of this compound in aquatic species stay insufficient. Therefore, the present research was designed to determine whether oxidative liver injury and inflammatory immune reactions in turbot (Scophthalmus maximus) fed an oxidized fish oil diet could be ameliorated by genistein supplementation.
METHODS: In this study, three dietary treatments were established: a fresh fish oil group (FFO), an oxidized fish oil group (OFO) in which fresh oil was completely replaced by oxidized oil, and a GEN40 group, where 40 mg/kg genistein was supplemented to the OFO basal diet. Juvenile turbot with an initial mean body mass of 10.00 ± 0.03 g were used in this study, and the feeding trial lasted 12 weeks.
RESULTS: As revealed by the results, hepatic mitochondrial impairment was induced in turbot by oxidized fish oil ingestion, as reflected by reduced cristae number, cristae disorganization, and concentric cristae formation, while a significant increase in hepatic superoxide anion abundance was also noted (P < 0.05). These mitochondrial alterations were partially alleviated by genistein supplementation, with which a marked decrease in superoxide anion levels was concurrently observed (P < 0.05). Moreover, the hepatic mRNA levels linked to inflammation, oxidative stress, and apoptosis were markedly upregulated in the OFO group (P < 0.05), yet declined in the GEN40 group (P < 0.05). Transcriptomic analysis revealed that after genistein supplementation in oxidized fish oil-based diets, the DEGs were predominantly enriched in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways such as the Peroxisome Proliferator-Activated Receptor (PPAR), calcium signaling, and adrenergic signaling pathways. It was further revealed by Gene Ontology (GO) enrichment analysis that the OFO group chiefly suppressed lipid catabolism and signal transduction, while activating the immune response. Compared with the FFO group, the genistein-treated group downregulated lipid metabolism and upregulated substance transport processes. Relative to the OFO group, it downregulated signal transduction and upregulated RNA-related catalytic activities. Moreover, methionine-S-sulfhydryl reductase B2 (msrb2) and heat shock protein 60 (hspd1) were identified as hub genes through Weighted Gene Co-expression Network Analysis (WGCNA) and were associated with the genistein-mediated alleviation of hepatic oxidative and inflammatory stress that was triggered by oxidized fish oil in turbot.
DISCUSSION: The above results confirmed that adding 40 mg/kg of genistein to an oxidized fish oil-based diet significantly alleviated hepatic oxidative stress and inflammatory injury mediated by the oxidized fish oil; besides msrb2 and hspd1 possibly served a critical function in this process.